Journal Article

Low Level of Lead Can Induce Phosphatidylserine Exposure and Erythrophagocytosis: A New Mechanism Underlying Lead-Associated Anemia

Won-Hee Jang, Kyung-Min Lim, Keunyoung Kim, Ji-Yoon Noh, Seojin Kang, Youn-Kyeong Chang and Jin-Ho Chung

in Toxicological Sciences

Volume 122, issue 1, pages 177-184
Published in print July 2011 | ISSN: 1096-6080
Published online April 2011 | e-ISSN: 1096-0929 | DOI: http://dx.doi.org/10.1093/toxsci/kfr079
Low Level of Lead Can Induce Phosphatidylserine Exposure and Erythrophagocytosis: A New Mechanism Underlying Lead-Associated Anemia

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Anemia is probably one of the most well-known toxic effects of lead. Previously, lead-induced anemia was considered to be from the inhibition of δ-aminolevulinic acid dehydratase participating in the heme biosynthesis. However, little is known whether lead could affect the destruction of erythrocyte, another important factor for anemia. In the present study, we demonstrated that lead could accelerate the splenic sequestration of erythrocytes through phosphatidylserine (PS) exposure and subsequently increased erythrophagocytosis. In freshly isolated human erythrocytes, Pb2+- induced PS exposure at relatively low concentrations (∼0.1μM) by inhibiting flippase, a key aminophospholipid translocase for the maintenance of PS asymmetry and adenosine triphosphate depletion appeared to underlie this phenomenon. Abnormal shape changes of erythrocytes and microvesicle generation and other triggers for the erythrophagocytosis were also observed in the Pb2+-exposed erythrocytes. In vitro data showed that human macrophage indeed recognized and phagocytosis PS-exposed erythrocytes. In good accordance with these in vitro results, the oral administration of Pb2+ increased PS exposure on erythrocytes in rat in vivo. In addition, reduction of hematocrit and hemoglobin and increased spleen weight were observed along with enhanced splenic sequestration of erythrocytes in the rats exposed to Pb2+ subchronically for 4 weeks through drinking water. In conclusion, these results suggest that Pb2+-induced anemia may be explained at least in part by increased PS exposure on erythrocytes, erythrophagocytosis, and splenic sequestration.

Keywords: erythrocyte; lead; anemia; phosphatidylserine exposure; phagocytosis

Journal Article.  4640 words.  Illustrated.

Subjects: Medical Toxicology ; Toxicology (Non-medical)

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